Tamsulosin is a pharmaceutical active substance from the group of antagonists of α1-adrenergic receptors, which are used for the treatment of functional disorders of the prostate. Tamsulosin is chemically (R)-5-(2-((2-(2-ethoxyphenoxy)ethyl)amino)propyl)-2-methoxybenzenesulphonamide (formula 1) and belongs to the groups of benzensulphonamides and sulphamoyl phenethylamines.

Tamsulosin is commercially marketed in a form of the hydrochloride of pure (R)-enantiomer and is used for the treatment of benign prostatic hyperplasia. According to the invention the term “tamsulosin” means the compound of formula (1) in a form of the hydrochloride salt whereas the compound in a non-salt form is named the tamsulosin base.
There is a constant need for the preparation of pharmaceutical active substances with a quality suitable for incorporation into a final medical product in technologically as simple and economical way as possible. Tamsulosin is a chiral molecule and its (R)-enantiomer is used as a therapeutic active substance. Providing an optically pure compound with a minimal portion of the undesired (S)-isomer is a serious technical problem being relatively difficult to solve because enantiomers cannot be separated by conventional chemical methods and separations.
Tamsulosin may be prepared according to the basic patent EP 34432 in which examples disclose first the preparation of a racemate which is further purified by column chromatography on a chiral matrix to obtain enantiomers.
Patent applications WO 03/37850 and WO 03/37851 disclose an alternative preparation of tamsulosin via synthesis of the crystalline racemic tamsulosin base which should be purified with expensive camphor-5-sulphonic acid. In WO 03/37850 such separation of final racemic tamsulosin base is explicitly reported, however, in the last step there is always a risk that chiral separation would not be complete and a product with a greater amount of the opposite enantiomer would be obtained.
In CZ 290.708 a process for the separation of racemic tamsulosin by using an acid is disclosed.
To avoid such separations, the optically pure (R)-5-(2-aminopropyl)-2-methoxybenzenesulphonamide (2) should be prepared.

(R)-5-(2-aminopropyl)-2-methoxybenzenesulphonamide (2) is known in the art as a key intermediate in the synthesis of tamsulosin. Processes for the synthesis of (R)-5-(2-aminopropyl)-2-methoxybenzenesulphonamide (2) have already been reported in the prior art. For example:
U.S. Pat. No. 5,447,958 discloses the synthesis of the compound (2). The starting product is (−)-2-(p-methoxyphenyl)-1-methylethylamine) whereby the synthesis thereof is not disclosed.
In EP 380144 the synthesis of the compound (2) starting with reductive amination of 5-acetonyl-2-methoxybenzenesulphonamide with R(+){tilde over (α)}-methyl benzylamine, followed by hydrogenesis. Synthesis of 5-acetonyl-2-methoxy benzenesulphonamide is not disclosed.
In CA 1,282,077 among other processes also the synthesis of the compound (2) is disclosed starting from (R)(−)-2-(p-methoxyphenyl)-1-methylethylamine without indicating the process of preparation of the latter.
It would be therefore desirable to develop alternative processes for a more straightforward preparation of (R)-5-(2-aminopropyl)-2-methoxybenzene sulphonamide, which does not require the optical resolution of intermediates, allowing the industrial preparation of this product to be simplified and, therewith, the production costs to be reduced.